Stroke and Systemic Embolism Prevention in Adult Participants With Atrial Fibrillation for Whom Oral Anticoagulation is Unsuitable (ROXI-INCLINE)

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 3

Conditions: Atrial Fibrillation (AF)

Treatments: Drug: REGN9933; Drug: REGN7508; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07430956

R9933-CVA-2495

2025-521618-25-00 (EU Trial (CTIS) Number)

2025

Details and patient eligibility

About

This study is researching 2 different experimental drugs called REGN7508 and REGN9933 (called "study drugs"). The study is focused on people who have atrial fibrillation, which means that the heart beats too fast and unevenly. When this happens, blood cannot move smoothly through the heart; it can slow down or pool in one spot, which can lead to the formation of blood clots.

REGN7508 and REGN9933 are designed to help stop blood clots forming in patients with atrial fibrillation. The aim of the study is to see how effective and safe REGN7508 and REGN9933, individually, are in preventing ischemic stroke or systemic embolism in people with atrial fibrillation who cannot or may choose to not take blood thinners.

The study is looking at several other research questions, including:

• What side effects may happen from taking REGN7508 or REGN9933
• How well does REGN7508 or REGN9933 lower the risk of having an ischemic stroke and/or systemic embolism compared to the placebo
• How well does REGN7508 or REGN9933 lower the risk of having a major health problem affecting heart and blood circulation compared to placebo
• How well does REGN7508 or REGN9933 lower the risk of death compared to placebo
• How much REGN7508 or REGN9933 is in the blood at different times
• Whether the body makes antibodies against REGN7508 or REGN9933 (which could make the study drugs less effective or could lead to side effects)

Enrollment: 2,628 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Has AF or flutter (paroxysmal or persistent), not considered to be secondary to a reversible cause

2. At moderate to high risk for stroke defined as:

   1. CHA2DS2-VA [C: Congestive heart failure; H: Hypertension; A2: Age ≥75 years (double points); D: Diabetes mellitus; S2: Stroke or TIA or Systemic embolism (double points); V: Vascular disease; A: Age 65-74 years] score ≥4 OR
   2. CHA2DS2-VA score of 3 AND at least 1 enrichment criteria as described in the protocol

3. Shared decision making between the participant and provider determining that the bleeding risk of Oral Anticoagulant (OAC) therapy outweighs the benefits, making the participant unsuitable for OAC therapy as described in the protocol

Key Exclusion Criteria:

1. Has a mechanical heart valve prosthesis (Note: transcatheter aortic valve replacement is not an exclusion)
2. Had an ischemic stroke within 2 days prior to randomization
3. Has persistent, uncontrolled hypertension (per investigator's discretion)
4. Has a history of Central Nervous System (CNS) bleeding within 30 days prior to randomization
5. Has a life expectancy less than 12 months
6. Has participated in a prior Factor XI (FXI) inhibitor study

Note: Other protocol-defined Inclusion/ Exclusion criteria apply

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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2,628 participants in 3 patient groups, including a placebo group

REGN7508

Experimental group

Treatment:

Drug: REGN7508

REGN9933

Experimental group

Treatment:

Drug: REGN9933

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo